Ethnobotanical survey and scientific validation of liver-healing plants in northeastern Morocco

Introduction Liver diseases represent a significant global health challenge, with primary causes including excessive alcohol consumption, infections, chemotherapy, and autoimmune disorders. Medicinal plants, due to their natural bioactive compounds, hold promise for developing effective treatments and preventive measures against liver ailments. This study aimed to document the use of herbal remedies in northeastern Morocco for liver diseases and correlate these uses with scientific evidence through a bibliometric analysis. Methods An ethnobotanical survey was conducted in remote communities of northeastern Morocco from October 2020 to January 2022. A total of 189 informants were interviewed using semi-structured questionnaires to gather information on local medicinal plants used for liver ailments. The data were analyzed using four ethnobotanical quantitative indices: use value (UV), familial use value (FUV), informant consensus factor (ICF), and fidelity level (FL). Additionally, a bibliometric analysis was performed to evaluate the scientific support for the ethnopharmacological uses documented. Results The survey identified 45 plant species from 26 different families used in the treatment of liver diseases. The most frequently utilized species were Cuminum cyminum L. (UV = 0.1065), Allium sativum L. (UV = 0.1015), Salvia officinalis L. (UV = 0.0761), Asparagus officinalis L. (UV = 0.0558), and Ziziphus lotus (L.) Lam. (UV = 0.0457). The Apiaceae family showed the highest familial use value (FUV = 0.1066), followed by Alliaceae (FUV = 0.1015). Liver congestion had the highest informant consensus factor (ICF = 0.83), followed by hepatic colic (ICF = 0.80). Bibliometric analysis revealed that 61% of the plants identified had documented pharmacological effects related to liver health. Discussion The study demonstrates that traditional knowledge in northeastern Morocco encompasses a rich diversity of medicinal plants used to treat liver diseases. The high ICF values indicate a strong consensus among informants on the efficacy of these remedies. The correlation between ethnopharmacological use and scientific validation for a significant portion of these plants suggests their potential as reliable therapeutic agents for liver conditions. However, further scientific investigations are necessary to confirm their efficacy and safety in clinical settings. This research contributes valuable information for future studies on the therapeutic potential of these plants. Conclusion This ethnobotanical survey provides a comprehensive database of medicinal plants used in northeastern Morocco for liver diseases. The findings highlight the potential of these plants in developing novel treatments for hepatic conditions, although further research is essential to substantiate their therapeutic claims.

Introduction: Liver diseases represent a significant global health challenge, with primary causes including excessive alcohol consumption, infections, chemotherapy, and autoimmune disorders.Medicinal plants, due to their natural bioactive compounds, hold promise for developing effective treatments and preventive measures against liver ailments.This study aimed to document the use of herbal remedies in northeastern Morocco for liver diseases and correlate these uses with scientific evidence through a bibliometric analysis.
Methods: An ethnobotanical survey was conducted in remote communities of northeastern Morocco from October 2020 to January 2022.A total of 189 informants were interviewed using semi-structured questionnaires to gather information on local medicinal plants used for liver ailments.The data were analyzed using four ethnobotanical quantitative indices: use value (UV), familial use value (FUV), informant consensus factor (ICF), and fidelity level (FL).Additionally, a bibliometric analysis was performed to evaluate the scientific support for the ethnopharmacological uses documented.

Introduction
The liver is one of the most critical organs in the human body, playing a pivotal role in several physiological functions, including the regulation of metabolic processes, maintenance of blood sugar levels, bile production, and detoxification of foods, water, drugs, and xenobiotics (Marcellin and Kutala, 2018).These functions are vital for sustaining overall health, as the liver processes everything that enters the body, ensuring that nutrients are metabolized correctly and harmful substances are neutralized.Given its extensive involvement in maintaining homeostasis, the liver is susceptible to various diseases, which can manifest as serious clinical syndromes such as jaundice, hepatitis, hepatocarcinoma, and cirrhosis.Because of its essential functions, the liver is often considered a reflection of an individual's overall health (Rinder et al., 2011).
Liver dysfunction is a significant global health problem, with a variety of causes that contribute to its widespread prevalence.These causes include excessive alcohol consumption, infections (notably viral hepatitis), the use of chemotherapeutic agents, exposure to toxic chemicals, and autoimmune disorders (Wei et al., 2022).The impact of liver diseases is profound, with global mortality rates reaching approximately 2 million deaths annually.Of these, 1 million deaths are attributed to complications arising from viral hepatitis and hepatocellular carcinoma, while another 1 million result from cirrhosis (Asrani et al., 2019).The growing burden of liver diseases has underscored the urgent need for effective therapeutic strategies, particularly in regions where access to conventional medical treatments is limited.
Medicinal plants have long been recognized as a valuable source of therapeutic agents, offering potential remedies for a wide array of health conditions, including liver diseases (Bhagawan et al., 2023a).The use of plants in traditional medicine is deeply rooted in human history, with ethnobotanical practices providing insights into natural remedies that have been utilized for centuries (Bhagawan et al., 2022;2023b;2024).In Morocco, traditional herbal medicine remains a cornerstone of healthcare, especially in rural and underserved areas.Recent ethnobotanical research indicates that a significant proportion of the Moroccan population-ranging from 60% to 80%-relies on medicinal plants to meet their healthcare needs (Jamila and Mostafa, 2014;Labiad et al., 2020;Alami Merrouni et al., 2021;Fakchich and Elachouri, 2021;Bencheikh et al., 2022;2023).This reliance is driven by several factors, including the high cost of conventional medications, limited access to adequate healthcare facilities, and socio-economic challenges, particularly in remote and underdeveloped regions (Bencheikh et al., 2021e;Fakchich and Elachouri, 2021).
The cultural heritage of North-Eastern Morocco, like that of other regions in the country, is steeped in a rich tradition of herbal medicine that dates back to the Arab influence in the 7th century.Over centuries, the indigenous population has developed and maintained extensive knowledge of medicinal plants, which forms the foundation of the region's traditional medical system.This knowledge is passed down orally from one generation to the next, ensuring the continuity of these traditional practices.However, this oral transmission is also a source of vulnerability.The absence of formal documentation and the lack of ethnobotanical archives pose significant threats to the preservation of this cultural heritage.As modern influences encroach and younger generations turn to contemporary medicine, there is a real risk that this indigenous medicinal knowledge, along with the phytogenetic resources it depends on, could be lost (Eddouks et al., 2017).
In Morocco, despite the widespread use of traditional medicine, there is a notable gap in ethnobotanical documentation, particularly concerning medicinal plants used for treating liver diseases.This lack of documented evidence limits the potential for scientific validation and integration of these traditional practices into modern healthcare systems.To address this gap, we propose a study aimed at documenting and analyzing the traditional knowledge related to medicinal plants used in rural areas of North-East Morocco for the treatment of liver diseases.The study will also seek to correlate these traditional uses with scientific evidence through a bibliometric review, thereby providing a comprehensive understanding of the therapeutic potential of these plants and contributing to the preservation of Morocco's ethnobotanical heritage.humid winters, the region has a Mediterranean climate zone, with average annual rainfall ranging from 100 mm in the south to 400 mm in the north.Additionally, the area has a number of protected areas and sites of biological and ecological interest, including Al Hoceima National Park, Benisnassen, Jbel Gorougou, Cap des Trois Fourches, Chekhar, Lalla Chafia, and Lalla Mimouna.In fact, these places had already been chosen because of their biological and ecological characteristics as well as their indigenous flora (Fennane, 2004;Fakchich and Elachouri, 2021).

Ethnobotanical data collection
The collection of ethnobotanical data on liver diseases was conducted between October 2020 and January 2022 across twelve rural communes located in five provinces of northeastern Morocco.Traditional knowledge was randomly selected from twelve stations studied through structured and semi-structured interviews using a questionnaire sheet with 189 local residents and 8 traditional herbalists participated.Verbal informed consent was gained from informants following verbal explanation of the study aims.The established best practice for ethnobotanical investigations, the International Society of Ethnobiology's Code of Ethics, was followed when conducting interviews (International Society of Ethnobiology, 2006).The questionnaire sheet utilized in this study has two sections: the first lists the respondents' demographic information, and the second lists their floristic and ethnic backgrounds.

Identification of specimens
We were able to transform the common names of plants identified during our ethnobotanical survey into their botanical names using some relevant references (Bellakhdar et al., 1991;Jamila and Mostafa, 2014).Subsequently, plant samples were collected from various vegetation sites across the northeastern region of Morocco.After the harvest, the botanical identification of the samples was carried out in the Laboratory of Bioresources, Biotechnologies, Ethnopharmacology and Health of the Faculty of Sciences of Mohammed first University, Oujda, Morocco, with the help of available herbaria and a number of essential references such as the catalogue of Moroccan plants and the practical flora of Morocco (Jahandiez and Maire, 1931;1932;1934;Fennane et al., 1999;2007;2014).After the samples were identified, specimens were placed in the Mohammed First University Herbarium in Oujda, Morocco.Using the World Flora Online (WFO) Plants database (https://wfoplantlist.org/),all scientific names were reviewed once more.Additionally, a group of flowering plants (angiosperms) known as Angiosperm Phylogeny Group III -2009 has been given credit for naming all plant families (A.P.G III, 2009).

Quantitative data analysis
To quantify the ethnobotanical information, we adopted a quantitative analysis using ethnobotanical indices such as the Medicinal Use Value (UV), the Family Use Value (FUV), Informant Consensus Factor (ICF), and the Fidelity Level (FL).

• Medicinal use value (UV)
We analyzed the medicinal use value of each plant species to identify the relative relevance of each plant species that is locally recognized to be utilized in herbal treatments.This index is calculated using the formula below (Tabuti et al., 2003): Where; UV: medicinal use value, U: number of citations per species, N: number of informants.The UV value will be larger if a plant has a high utilization ratio, indicating that the plant is significant, however if there are few utilization ratios, it will be near to zero.

• Botanical Family Use Value (FUV)
We used the family use value index to analyze the association between botanical families and users of taxa that correspond to these families.This index is equal to the mean total use value of each species in the family (Hoffman and Gallaher, 2007).

FUV UV N
Where; FUV is the family use value, UV is the utility value of the family's species, and N is the number 173 of species in the family.

• Informant Consensus Factor (ICF).
The ICF demonstrates the uniformity of traditional knowledge exchange amongst informants regarding the usage of plants to cure different types of diseases.The following formula was used to determine ICF (Bencheikh et al., 2021e).

ICF
Nur − Nt Nur − 1 Where; Nur denotes the number of use-reports for an ailment category and Nt denotes the total number of plants used by all informants for that illnesses category.The ICF values range between 0 and 1, with values close to 0 indicating that the herbs were picked at random or that there was no exchange of information about plant usage within the population.Furthermore, ICF values close to 1 indicate a clear selection of medical species and information sharing about their use in the population.

• Fidelity Level (FL).
The level of fidelity (FL) identifies a plant species' ability to effectively combat a certain disease.FL was determined using the formula below (Sreekeesoon and Mahomoodally, 2014). Where; Lu denotes the total number of interviewers who cited all uses of the particular species for the therapies of all liver pathologies, and Ip represents the number of individuals who used a particular species for a specific type of liver disease.

Pharmacological validation
A bibliographic search was conducted to identify the biological activities of identified plants against liver disease, by the mean of the following databases: PubMed, Science Direct, Google Scholar, Scopus and Web of Science with keywords like "liver disease," "liver disease," "Liver failure," "hepatitis," "Jaundice," and "Hepatoprotective" combined with the scientific name of each plant.

Informants' sociodemographic profile
A total of 197 informants, including 189 non-specialists and 8 herbalists interviewed for this study.These interviewees are spread over twelve rural stations in five provinces of North-East Morocco (Table 1).The socio-demographic profile of the participants in this  Bencheikh et al., 2021e;Hachlafi et al., 2022).The discomfort of the younger generation, which tends not to accept popular medicine due to the effect of exotic culture, and the influence of lifestyle modernization can be used to explain the gradual loss of traditional knowledge about medicinal plants (Sargin et al., 2015).The fact that there were fewer informants over the age of 65 (14.21%) is a reflection of the depth of traditional knowledge being lost as rural elders pass away.
In terms of educational attainment, the findings revealed that 38.07% of the informants are illiterate, followed by the categories of secondary and primary education, with percentages, respectively 35.03% and 19.29%, and lastly the university level, with a percentage of 7.61%.These findings are consistent with those of other ethnobotanical studies conducted in various regions of Morocco (Khouchlaa et al., 2017b;Bencheikh et al., 2021e;Hachlafi et al., 2022).The study area's rising illiteracy rate may be caused by the fact that poverty is still pervasive in the rural areas examined.This is indicated in our results, where the majority of respondents had a low socio-economic level (41.11% unemployed, and 45.17% between 500 and 2000 DH/month).
There are differences in how the people in this area feel about treating liver illness.The results shown in Table 2 demonstrate the extreme variety of usage patterns.In fact, the majority of interviews indicated that traditional medicine was their first choice of treatment when they were ill, with a percentage of 51.27%, followed by the use of conventional and herbal medicine in second place, with a percentage of 38.58%, and exclusively modern medicine in third place, with a percentage of 10.15%.Access to modern medication is hampered by a lack of health facilities and trained medical personnel, a lack of infrastructure, particularly paved roads, a lack of transportation options, a lack of logistical support, and the high expense of treating liver disease with modern medicine (El Hassani et al., 2013;Eddouks et al., 2017).The aforementioned factors all strongly encourage rural populations to switch to traditional healthcare, especially the usage of medicinal herbs.

Diversity of plant species used to treat liver diseases
This study recorded the use of 45 medicinal plants, spread across 26 families and 43 genera, for the treatment of liver disease in the study area.Traditional information on the applications of these plants has been developed (Table 3), including the use value, Frontiers in Pharmacology frontiersin.org07 Bencheikh et al. 10.3389/fphar.2024.1414190scientific name, botanical family, popular names, traditional uses, parts utilized, preparation procedure, and mode of administration for each medicinal species.

Frequency of families and their use value
As indicated in Table 4, a total of 26 botanical families were used in rural areas of North-East Morocco for the treatment of liver pathologies.However, the families most used are Lamiaceae (7 species; 6 genera) in the first position, followed by Asteraceae (5 species; 4 genera), Apiaceae (4 species; 4 genera), Fabaceae (3 species; 3 genera), Myrtaceae, Poaceae, Rosaceae and Zingiberaceae with (3 species; 3 genera) for each.There are only one species and one genus for the other families.Similarly, the Lamiaceae, Asteraceae, and Apiaceae botanical families are the ones that are most prevalent in Mediterranean countries (Benítez et al., 2010;Savo et al., 2011).The predominance of the Asteraceae family in the traditional treatment of liver disease has already been confirmed by an ethnobotanical study carried out in the Maritime region of Togo (Kpodar et al., 2016).
Families with high FUV are Apiaceae (0.1066), Alliaceae (0.1015), Asparagaceae (0.0558), and Piperaceae (0.0355) (Table 4).However, there aren't many species in these groups to represent them.It appears that the value of using ethnobotanical families is not dependent on their particular wealth but rather on the significance and value of the use of the individual species (Najem et al., 2019).Additionally, these families' significant FUV would be mostly dependent on their abundance of bioactive compounds, which would confer multiple benefits such as antimicrobial, anti-allergic, anti-oxidant, and antiinflammatory properties (Bencheikh et al., 2022).Lam.(UV = 0.0457) (Table 3).These five species made up 27.84% of all use ratios, while the other 40 species only made up 72.16% of all use ratios.Similar studies conducted in other nations have shown that high utilization values have been attained for plants other than those in the current study (Kotoky and Das, 2008;Kpodar et al., 2016).This difference in species similarity could be explained by the difference in bioclimate between countries, which will favor the difference in the abundance of certain plant species from one country to another.In addition, geographic distance between countries has a direct impact on the traditional cultures of indigenous peoples, as evidenced by Alami Merrouni et al. ( 2021), in which they demonstrated that the increase in distance between countries is accompanied by the increase in the difference in the cultures of these countries and vice versa.Thus, all these factors can lead to differences between countries in the use of plant species to treat a particular health condition.These five medicinal plants were frequently utilized in traditional Moroccan medicine to cure a wide range of illnesses:

Most used plants species to treat liver diseases according to use value index
Cuminum cyminum L.: This Apiaceae family medicinal plant was one of the first plants grown in Asia, Africa, and Europe (Alsnafi, 2017).Since antiquity, C. cyminum seeds have persisted in popularity as culinary seasonings and are widely utilized in folk therapy across a variety of geographic regions.This plant, called in Morocco as "Kammun", is frequently used conventionally to treat digestive system issues, including diarrhea (Jamila and Mostafa, 2014).According to the analysis of the data collected during our investigation, C. cyminum is the most widely used to treat liver pathologies in the North-Eastern Moroccan population with a usage value of 0.1065.Indeed, the seeds of C. cyminum, in decoction or infusion, are used by the study population as treatment of jaundice, and hepatitis, and thus for liver detoxification.In Ayurveda (former Indian therapeutic system), seeds of C. cyminum are traditionally used against jaundice and to improve liver function (Andallu and Ramya, 2007;Johri, 2011).
Allium sativum L.: This plant, called locally as "Thouma" in Morocco, is one of the earliest known to have been cultivated (Thomson and Ali, 2003).Traditional Moroccan medicine makes extensive use of garlic to cure and prevent a wide range of illnesses, including cancer, lung disease, hypertension, diabetes, microbiological infections, infertility, and problems with the kidneys (Fakchich and Elachouri, 2021).According to the results of our investigation, this plant is classified according to its use value in the second position as the plant most used to treat liver diseases in the northeast of Morocco.Indeed, the leaves and bulb of this plant in decoction or infusion are widely recommended by the inhabitants of the study area to fight against liver cancer and hepatitis, and thus declared that it has hepatoprotective effects.Furthermore, it has been reported that portions of this plant are commonly used to heal liver problems in Togo's Maritime region (Kpodar et al., 2016).The bulb of plant is often used to treat jaundice in the southern region of Algeria (Bendaif et al., 2021).
Salvia officinalis L.: This round perennial shrub belongs to the Lamiaceae family and is called to as "Salmiya" in the Oriental area of Morocco.It is indigenous to the Middle East and the Mediterranean, although it has since become naturalized everywhere (Ghorbani and Esmaeilizadeh, 2017).In Morocco, the aerial part of S. officinalis is used to handle gastrointestinal problems, metabolic disorders, and renal ailment (Bencheikh et al., 2021e;Fakchich and Elachouri, 2021).Based on the findings of the current investigation, this plant is classified among the three most used medicinal species in the study area for the treatment of liver diseases.Indeed, the leaves and stems of S. officinalis, in decoction or infusion are widely used in rural areas of north-eastern Morocco to prevent and treat jaundice, hepatitis, and liver cancer, and thus to detoxify the liver.In the middle Oum Rbia region of Morocco, leaves and whole plant decocted were used for liver problems (Ben Akka et al., 2019).In addition to these local uses, in traditional South-West Algerian medicine, the flowers of this plant were also used to treat liver symptoms (Benarba, 2016).
Asparagus officinalis L.: Since ancient times, asparagus, a perennial herbaceous plant of the Asparagaceae family, has been  utilized extensively in food and medicinal.This plant is called « Sekoum» in Morocco, is used to treat various ailments such as respiratory diseases, digestive problems, kidney diseases, liver diseases and diabetes (Alami Merrouni and Elachouri, 2021;Fakchich and Elachouri, 2021;Bencheikh et al., 2022).In our study, asparagus is ranked fourth among the most cited plants for the treatment of liver patients.In fact, this plant's leaves and stems are frequently used to treat biliary issues, liver stones, hepatitis, and jaundice.
Ziziphus lotus (L.) Lam.: The majority of Africa, numerous Asian nations, including China, Iran, and South Korea, as well as several European nations, including Cyprus, Spain, and Greece, are all home to this medicinal plant (Adeli and Samavati, 2014;Bencheikh et al., 2021d).In Morocco, Z. lotus is locally known as "Sedra," and "Nbeg" for its fruits, and is widely found in arid and semi-arid areas (Bencheikh et al., 2019).Plant parts were traditionally used to combat various health problems such as sedation, anxiety, urinary problems, diabetes, skin infections, scarring, and bronchitis (Khouchlaa et al., 2017a;Bencheikh et al., 2021e;Fakchich and Elachouri, 2021).As per the findings of our survey, Z. lotus in rural parts of North-East Morocco, is one of the top five plants used to treat liver disorders such as jaundice, hepatic colic, and hepatitis.Furthermore, the fruits of this medicinal plant are traditionally used to treat lung diseases, jaundice, and as an emollient in El Hammadia, Algeria (Bendaif et al., 2021).

Ethnic medicinal characteristics
In this study, different parts of plants are used as medicines to treat liver problems in rural areas of North-East Morocco (Figure 2).Thus, on the basis of calculating the percentage of use of each part (%), the leaves (50.82) appear to be the most commonly utilized for the treatment of liver illnesses in the study area, followed by fruits (21.3), stems (9.84), whole plants (6.56), the seeds, and the flowers (4.92) for each, and finally the bulbs (1.64).The leaves are both a source of photochemical reactions and a repository of organic stuff created from them, which explains why they are used so frequently (Bencheikh et al., 2021e).In addition, it is important to avoid pulling out the entire plant or picking up the roots of the plants, as this will promote deforestation and put the species at risk (Kadir et al., 2013).On the contrary, the use of leaves contributes to the conservation and sustainable use of the plant.
As seen in Figure 3, various techniques are used in rural North-East Morocco to make alternative therapies for treating liver disease.Nevertheless, with a percentage of 48.61%, decoction remains the most commonly employed method of preparation, followed by infusion (29.17%), maceration (6.94%), powder and preparation in the diet (5.56% for each), and finally oils with 4.17%.The preparation technique is frequently correlated with the type of use (external or internal); typically, external usage involves the use of a mask, massage, or suppositories, while internal use involves the use of decoction, infusion, maceration, and other techniques (Eddouks et al., 2017).Decoction's supremacy may thus be explained by the fact that it allows for the capture of the greatest amount of bioactive molecules and reduces or eliminates the toxic effects of some recipes (Noureddine et al., 2022).

Hepatic ailments categories and their informant consensus factor (ICF) values
In this study, we identified eight liver pathologies that were treated with medicinal plants in rural areas of North-East Morocco (Figure 4).The ICF values of the plant species cataloged in this investigation extended from a minimum of 0.25 to a maximum of 0.83.(Figure 5).This index has the highest value for liver congestion (ICF = 0.83), followed by hepatic colic (ICF = 0.80), liver cancer (ICF = 0.69), liver detoxification (ICF = 0.67), hepatitis (ICF = 0.66), jaundice (ICF = 0.54), liver stone (ICF = 0.50), and bile problems with ICF = 0.25.High values (around 1) of this index for liver congestion, hepatic colic, and liver cancer suggest that a small number of species were employed by many informants, reflecting a high level of consensus on the use of plants in the management of these illnesses.The low accord between both interviews was Category of hepatic illness and their informant consensus factor (ICF).
Frontiers in Pharmacology frontiersin.orgwitnessed for biliary problems.This could be attributed to a lack of interaction and knowledge exchange among individuals (Al-Qura'n, 2005).

Fidelity level (FL)
According to the corresponding level of fidelity, we categorized the medicinal plants used to treat liver illness in Table 5.According to our findings, the level of fidelity of plant species for a particular liver condition ranged between 9.09% and 100%.Concerning   is the most important for liver stone and bile problems.The importance of these plants for the treatment of liver diseases in the study area could be due to their wide use in traditional Moroccan medicine to treat various diseases (Fakchich and Elachouri, 2021).

Pharmacological confirmation data of the medicinal plants
The current ethnobotanical fieldwork confirmed that the inhabitants of northeastern Morocco has extensive ethnobotanical information concerning the use of herbal remedies in the treatment of liver conditions.These conventional data, which detailed a wide variety of quantitative factors, were particularly intriguing for the goal of bioprospecting to identify novel drugs to cure liver pathological conditions.It could be worthwhile to look up these plants' pharmacological properties in the literature.According to the results of our bibliographic survey, of the 46 plant species registered for the treatment of liver diseases in the study area, 28 plant species from 20 botanical families have already been pharmacologically validated for liver diseases (Table 6).It can be concluded that the majority of them significantly reduce the risk of liver disorders.These findings demonstrated the potential of ethnobotanical knowledge as a preferable traditional database for plant species with beneficial therapeutic effects connected to liver illnesses.The pharmacological data collected for the plants selected during our survey were grouped in the Table 6.
According to the results of our ethnobotanical survey, C. cyminum L. (UV = 0.1065), A. sativum L. (UV = 0.1015), S. officinalis L. (UV = 0.0761), Asparagus officinalis L. (UV = 0.0558), and Z. lotus (L.) Lam.(UV = 0.0457) are the medical species commonly used in Northeastern Morocco for the treatment or prevention of liver problems.To support the use of these plants in conventional medicine, it may be interesting to further explore and discuss their pharmacological properties related to liver problems.To this goal, we shall explore the pharmacological potential of these herbs in the following paragraphs to validate their benefits against liver diseases: Allium sativum L. is ranked as the second most used species (UV = 0.1015) for the treatment of liver diseases.According to ethnobotanical findings, this plant is widely used in rural areas of northeastern Morocco for its hepatoprotective effect, against liver cancer, and viral infections (hepatitis).The leaves and bulb of A. sativum have demonstrated antioxidant and hepatoprotective effects against ethanol-induced hepatotoxicity in rats (Nencini et al., 2010).Indeed, the administration of an extract of the leaves or bulbs of A. sativum At a dose of 250 mg/kg, the Glutathion reductase (GR), catalase (CAT), and superoxide dismutase (SOD) activities were restored, and the levels of malondialdehyde, ascorbic acid, and glutathion were reduced and oxidized in the liver tissue of rats exposed to ethanol (Nencini et al., 2010).A study also discovered that A. sativum has a cytoprotective impact in HepG2 cells submitted to mycotoxines, specifically Beauvericin, α-Zearalenol and β-Zearalenol (Juan-García et al., 2021b).The presence of antioxidant compounds, according to the authors, is responsible for this cytoprotective effect, which involves the activation of defensive pathways as an enzymatic defence mechanism from within cells, the control of the cell cycle, and cell death, all of which can be provoked by these mycotoxines (Juan-García et al., 2021b).Another research revealed that an aqueous extract of garlic bulbs reduces alloxane elevation of biological parameters of liver and kidney functions in rats (Aprioku and Amah-Tariah, 2017b).
According to prior study, garlic includes a number of bioactive components such as organosulfur compounds, saponins, and phenolic compounds (Bradley et al., 2016;Diretto et al., 2017).
Frontiers in Pharmacology frontiersin.org22 Bencheikh et al. 10.3389/fphar.2024.1414190Mansingh et al., 2018).These compounds were discovered to be related to the plant's powerful antioxidant and antitumor ability (Bagul et al., 2015).Asparagus officinalis L. this plant is ranked third among the plants most commonly used for the treatment of liver diseases by the Moroccan population.It is frequently used to treat biliary problems, hepatic stones, hepatitis, and jaundice, as shown in Table 3.It has been reported that the aqueous and ethanolic extract of A. officinalis have hypolipidemic and hepatoprotective effects in mice fed a high-fat diet (Zhu et al., 2010).According to the findings of this study, daily treatment of 200 mg/kg of either ethanolic or aqueous extract for 8 weeks enhanced lipid parameters, transaminase (Alanine and Aspartate) activity, superoxide dismutase (SOD) and antioxidant capacity, and hepatic malondialdehyde levels.In addition, an in vivo research indicate that the aqueous extract of A. officinalis roots has protective properties on cadmium chloride-induced liver injury in rats (Abedi et al., 2018).This investigation found that treatment by aqueous extract of A. officinalis roots at 200 and 400 mg/kg for 28 days significantly restored liver biomarkers in cadmium chloride poisoned rats.Several phytochemical investigations have revealed that the main bioactive compounds found in asparagus include phenolic compounds, sterols, and saponins (Jang et al., 2004;Fuentes-Alventosa et al., 2013).Asparanin A, Asparoffin C, Asparoffin D, Asparenyol, Gobicusin B, Protodioscin and 1-methoxy-2-hydroxy-4-[5-(4hydroxyphenoxy)-3-penten1-ynyl] phenol are the main phytochemicals found in asparagus, with Rutin (Quercetin 3rutinoside) as the major compound (Figure 5) (Fan et al., 2015).These compounds' antioxidant action is well-known (Sun et al., 2007;Solana et al., 2015;Slatnar et al., 2018), that may contribute in the hepatoprotective effects of the plant.
Salvia officinalis L. This plant is widely used in folk medicine in North East Morocco to treat liver failure.It is ranked fourth of the most commonly used plants, with a use value of 0.0761.According to our findings, various parts of this plant have traditionally been used to treat jaundice, hepatitis, and liver cancer in the study site.Several preclinical investigations on plant parts were carried out to examine its medicinal qualities for liver failure.In fact, 8 weeks of daily administration of S. officinalis essential oil at 4 mg/kg enhanced hyperlipidemia, hepatic, and renal lesions in mice fed a high-fat diet (Koubaa-Ghorbel et al., 2020b).This effect of S. officinalis essential oil was more effective than that of simvastatin (standard drug for this purpose).In addition, daily intake of 15 mg/kg of the essential oil of S. officinalis showed a protective effect against vanadiuminduced hepatotoxicity in Wistar rats (Koubaa et al., 2021b).The treatment of rats with 200 mg/kg of S. officinalis aqueous extract for 15 days showed protective effects against ethanol-induced hepatotoxicity (Jedidi et al., 2022b).According to the same authors, this effect is reflected in the improvement of plasma transaminase activity and the restoration of hepatocyte structure in rats poisoned with ethanol.Besides, it was shown that administering a hydroalcoholic extract of S. officinalis at a dose of 250 mg/kg protected rats from isoniazid-induced hepatotoxicity (Shahrzad et al., 2014b).Furthermore, a previous investigation showed that an ethanolic extract of S. officinalis leaves protects human HepG2 cells from hydrogen peroxide and 2,3-dimethoxy-1,4-naphthoquinone-induced DNA damage (Kozics et al., 2013b).
Ziziphus lotus (L.) Lam.According to our ethnobotanical study conducted in several parts of the Moroccan North-East, this plant ranks sixth among the most commonly utilized herbs to cure liver disorders.Indeed, the leaves and fruits of this plant were utilized to treat jaundice, hepatic colic, and hepatitis in the research region.Previous pharmacological work has demonstrated that Z. lotus extracts exert hepatoprotective effects at the preclinical stage.In a rat investigation, an aqueous extract of Z. lotus fruits was found to have hepatoprotective properties against CCl 4induced liver damage (Bencheikh et al., 2019).The findings of this study indicate that administration of aqueous extract of Z. lotus fruits at doses of 200 and 400 mg/kg restored the biochemical parameters (liver biomarkers) altered during hepatotoxicity induced by CCl 4 injections in rats.Similarly, it has been reported that treatment of rats with the aqueous extract of Z. lotus fruit at doses of 200 and 400 mg/kg protects the liver and kidney from gentamicin poisoning (Bencheikh et al., 2021b).In the literature, it has been well demonstrated that the hepatotoxicity caused by the agent CCl 4 and gentamicin is related to the oxidative stress caused by these chemical compounds (Lin and Huang, 2000;Achuthan et al., 2003).In this context, several authors confirm that the use of natural antioxidants to fight against the oxidative stress caused by CCl 4 and gentamicin is the best strategy to prevent hepatotoxicity produced by these hepatotoxic substances (Bencheikh et al., 2021a;Bouhrim et al., 2021;Ouahhoud et al., 2021b).Extracts of Z. lotus fruits are high in phenolic compounds such as Rutin, Naringin, Chlorogenic acid, Rosmarinic acid, Quercetin, Catechin, Epicatechin, Sinapic acid, Resveratrol, and Caffeic acid, according to phytochemical research (Figure 6) (Marmouzi et al., 2019;Bencheikh et al., 2021c;2021d).These photochemical compounds thanks to their antioxidant powers could be responsible for the hypatoprotective effects.

Conclusion
This ethnobotanical study reveals that locals in remote areas of northern Morocco possess extensive traditional knowledge about using medicinal plants to treat liver diseases, reflecting the region's floristic richness.The findings demonstrate the potential of these herbs in addressing liver-related health issues within these communities.However, caution is necessary when using these remedies.The study is limited by its small sample size and lack of a control group, which may affect the robustness of the conclusions.
Further research is essential to evaluate the pharmacological benefits and phytochemical components of these plants, identify active ingredients, and confirm their clinical efficacy.Additionally, safety data are needed to standardize dosages and ensure safe use.Addressing these limitations will help in the development of effective medications derived from these medicinal plants for liver disease treatment.
In this work, we inventoried 45 different medicinal plants that are utilized to treat liver ailments in rural areas of North Eastern Morocco.Nevertheless, the most widely used plants for the treatment of liver diseases are Cuminum cyminum L. (UV = 0.1065), followed by Allium sativum L. (UV = 0.1015), Salvia officinalis L. (UV = 0.0761), Asparagus officinalis L. (UV = 0.0558), and Ziziphus lotus (L.)

FIGURE 2
FIGURE 2Distribution of plant parts by the percentage of use (%).

FIGURE 3
FIGURE 3Distribution of preparation methods according to percentages of use.

FIGURE 5
FIGURE 5Main components found in Allium sativum L. and Asparagus officinalis L.

TABLE 1
Number of informants for each locality.

TABLE 2
Socio-demographic characteristics of informants.Medicinal plants used in the study area for the treatment of liver ailments.

TABLE 3 (
Continued) Medicinal plants used in the study area for the treatment of liver ailments.
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TABLE 4
Distribution of botanical medicinal families according to species and genera.FUV: Family Use Value.

TABLE 3 (
Continued) Medicinal plants used in the study area for the treatment of liver ailments.
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TABLE 5
Fidelity level values of medicinal plants for each category of liver illness.

TABLE 5 (
Continued) Fidelity level values of medicinal plants for each category of liver illness.Pharmacological outcomes of medicinal plants cited by locals to cure liver ailments.

TABLE 6 (
Continued) Pharmacological outcomes of medicinal plants cited by locals to cure liver ailments.

TABLE 6 (
Continued) Pharmacological outcomes of medicinal plants cited by locals to cure liver ailments.

TABLE 6 (
Continued) Pharmacological outcomes of medicinal plants cited by locals to cure liver ailments.

TABLE 6 (
Continued) Pharmacological outcomes of medicinal plants cited by locals to cure liver ailments.

TABLE 6 (
Continued) Pharmacological outcomes of medicinal plants cited by locals to cure liver ailments.

TABLE 6 (
Continued) Pharmacological outcomes of medicinal plants cited by locals to cure liver ailments.

TABLE 6 (
Continued) Pharmacological outcomes of medicinal plants cited by locals to cure liver ailments.